Investigation of Phytochemicals as Anti-Alzheimer's Agents: An In Silico Study.

is a medicinal plant that has been known for years and is used as an Ayurvedic medicine. This plant has great potential in treating various types of brain diseases. Phytochemicals present in this plant act as antioxidants by maintaining synaptic plasticity and preventing neuronal loss. Cannabidiol (CBD) and Tetrahydrocannabinol (THC) are both beneficial in treating Alzheimer's disease by increasing the solubility of Aβ42 amyloid and Tau aggregation. Apart from these therapeutic effects, there are certain unknown functions of these phytochemicals in Alzheimer's disease that we want to elucidate through this study. In this research, our approach is to analyze the effect of phytochemicals in on multiple culprit enzymes in Alzheimer's disease, such as AChE (Acetylcholinesterase), BChE (Butyrylcholinesterase), γ-secretase, and BACE-1. In this study, the compounds were selected by Lipinski's rule, ADMET, and ProTox based on toxicity. Molecular docking between the selected compounds (THCV, Cannabinol C2, and Cannabidiorcol) and enzymes mentioned above was obtained by various software programs including AutoDock Vina 4.2, AutoDock, and iGEMDOCK. In comparison to Donepezil (BA = -8.4 kcal/mol, Ki = 1.46 mM), Rivastigmine (BA = -7.0 kcal/mol, Ki = 0.02 mM), and Galantamine (BA = -7.1, Ki = 2.1 mM), Cannabidiorcol (BA = -9.4 kcal/mol, Ki = 4.61 mM) shows significant inhibition of AChE. On the other hand, Cannabinol C2 (BA = -9.2 kcal/mol, Ki = 4.32 mM) significantly inhibits Butyrylcholinesterase (BuChE) in comparison to Memantine (BA = -6.8 kcal/mol, Ki = 0.54 mM). This study sheds new light and opens new avenues for elucidating the role of bioactive compounds present in in treating Alzheimer's disease.